EGF-receptor targeted liposomes with boronated acridine: growth inhibition of cultured glioma cells after neutron irradiation.

Purpose: To study survival of cultured U-343MGaCl 2:6 glioma cells after incubation with boron-containing liposomes targeting the epidermal growth factor receptor following neutron irradiation.

Materials And Methods: Epidermal growth factor-tagged liposomes were loaded with water-soluble boronated acridine developed for boron neutron capture therapy, (BNCT). Cellular uptake and distribution were studied.

An aminoacridine derivative for radionuclide therapy: DNA binding properties studied in a novel cell-free in vitro assay.

Radiolabelled DNA-binding compounds can be used to increase the efficiency of radionuclide cancer therapy of disseminated disease. In this work, the aminoacridine compound N-[3-(acridine-9-ylamino)-propyl]-3-iodobenzamide (A3) labelled with the Auger-emitting nuclide 125I using Chloramine-T was studied. Optimal labelling conditions of 125I-A3 were investigated and the interaction with DNA was studied using a novel cell-free in vitro assay with naked human genomic DNA in agarose plugs.

Trastuzumab-conjugated boron-containing liposomes for tumor-cell targeting; development and cellular studies.

The goal of the present study was to investigate HER-2-targeted boron-containing liposomes as a potential drug delivery vehicle for boron neutron capture therapy (BNCT). Trastuzumab was conjugated to the distal end of PEG-DSPE-NHS in micelles and the Trastuzumab-PEG-DSPE were then transferred to preformed liposomes, either empty or loaded with water soluble boronated acridine (WSA), using the micelle transfer method. The final conjugates were referred to as Trastuzumab-liposome and Trastuzumab-liposome-WSA.

Introductory experiments on ligand liposomes as delivery agents for boron neutron capture therapy.

Liposomes are, when coupled to receptor ligands, candidates for receptor mediated delivery of boron for tumour therapy since they have capacity to deliver large amounts of boron per receptor interaction. With EGF-liposomes we present a pegylated ligand liposome delivery vehicle, containing water soluble boronated phenanthridine, WSP1, or water soluble boronated acridine, WSA1, for EGFR targeting. In the case of WSA1 a ligand dependent uptake was obtained and the boron uptake was as good as if free WSA1 was given.

Ligand liposomes and boron neutron capture therapy.

Boron neutron capture therapy (BNCT) has been used both experimentally and clinically for the treatment of gliomas and melanomas, with varying results. However, the therapeutic effects on micro-invasive tumor cells are not clear. The two drugs that have been used clinically, p-boronophenylalanine, (BPA), and the sulfhydryl borane, (BSH), seem to be taken up preferentially in solid tumor areas but it is uncertain whether enough boron is taken up by micro-invasive tumor cells.

Tumor-cell targeted epiderimal growth factor liposomes loaded with boronated acridine: uptake and processing.

Purpose: The aim of this work was to investigate the cellular binding and processing of polyethylene glycol-stabilized epidermal growth factor (EGF) liposomes. The liposomes were actively loaded with water-soluble boronated acridine (WSA), primarily developed for boron neutron capture therapy.

Methods: The uptake, internalization, and retention of EGF-liposome conjugates were studied in two cultured monolayer cell-lines, A-431 and U-343, with regard to the nuclide-label on the targeting agent, the carrier, and the load.

Development of EGF-conjugated liposomes for targeted delivery of boronated DNA-binding agents.

Liposomes are of interest as drug delivery tools for therapy of cancer and infectious diseases. We investigated conjugation of epidermal growth factor, EGF, to liposomes using the micelle-transfer method. EGF was conjugated to the distal end of PEG-DSPE lipid molecules in a micellar solution and the EGF-PEG-DSPE lipids were then transferred to preformed liposomes, either empty or containing the DNA-binding compound, water soluble acridine, WSA.